7-137020404-A-G

Variant names:

• chr7-137020404-A-G
• rs1378650
• ENST00000439694.6:n.655+11501T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000439694.6(ENSG00000234352):​n.655+11501T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,582 control chromosomes in the GnomAD database, including 23,050 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (23049 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: ENSG00000234352 ENST00000439694.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 6 publications found

Genes affected

ENSG00000234352 (HGNC:):

CHRM2 (HGNC:1951): (cholinergic receptor muscarinic 2) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine to these receptors and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.*4138A>G		downstream_gene_variant		ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.*4138A>G		downstream_gene_variant			NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81404 AN: 151462 Hom.: 23023 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.537 AC: 81465 AN: 151580 Hom.: 23049 Cov.: 31 AF XY: 0.532 AC XY: 39396 AN XY: 74040

African (AFR) AF: 0.629 AC: 26020 AN: 41392

American (AMR) AF: 0.409 AC: 6219 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1957 AN: 3466

East Asian (EAS) AF: 0.102 AC: 525 AN: 5124

South Asian (SAS) AF: 0.267 AC: 1289 AN: 4826

European-Finnish (FIN) AF: 0.627 AC: 6596 AN: 10526

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37062 AN: 67752

Other (OTH) AF: 0.535 AC: 1125 AN: 2102

Alfa AF: 0.455 Hom.: 1925

Bravo AF: 0.527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1378650; hg19: chr7-136705151;